Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer.
Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer.
复制标题
成纤维细胞来源的CXCL 12/SDF-1α促进CXCL 6分泌，并通过PI 3 K/Akt/mTOR通路协同增强结肠癌的转移潜力。
DOI：
10.3748/wjg.v23.i28.5167
复制
发表时间：
2017-07-28
影响因子：
4.3
通讯作者：
Qi JB
中科院分区：
文献类型：
--
作者：
Ma JC;Sun XW;Su H;Chen Q;Guo TK;Li Y;Chen XC;Guo J;Gong ZQ;Zhao XD;Qi JB
探讨CXCL 12和CXCL 6影响结肠癌转移潜能的机制及结肠癌与基质细胞的内在联系。Western blotting检测结肠癌细胞和间质细胞中CXCL 12和CXCL 6的表达。采用酶联免疫吸附试验、增殖和侵袭实验检测CXCL 12和CXCL 6对结肠癌细胞和人脐静脉内皮细胞（HUVECs）增殖和侵袭的协同作用。血管生成实验检测HUVECs与肿瘤细胞及基质细胞相互作用后的血管生成情况。我们最终研究了参与结肠癌转移过程的CXCL 12对PI 3 K/Akt/mTOR信号转导的激活。CXCL 12在DLD-1癌细胞和成纤维细胞中表达。结肠癌细胞和HUVECs的CXCL 6分泌水平被CXCL 12来源的成纤维细胞显著促进。CXCL 6和CXCL 2可显著促进HUVEC增殖和迁移（P < 0.01）。CXCL 6和CXCL 2能促进HUVECs与成纤维细胞和结肠癌细胞共同培养时的血管生成（P < 0.01）。CXCL 12还增强了结肠癌细胞的侵袭。基质细胞来源的CXCL 12通过激活PI 3 K/Akt/mTOR通路促进CXCL 6的分泌水平并协同促进结肠癌的转移。成纤维细胞来源的CXCL 12促进结肠癌细胞CXCL 6的分泌，CXCL 12和CXCL 6通过PI 3 K/Akt/mTOR信号通路协同调节结肠癌细胞的转移。阻断该通路可能是结肠癌患者潜在的抗转移治疗靶点。
To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/mTOR signaling by CXCL12 involved in the metastatic process of colon cancer. CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration (P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells (P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/mTOR pathway. Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells, and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/mTOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer.
登录
查看更多内容
影响因子：
4.6
作者：
Costantini S;Romano G;Rusolo F;Capone F;Guerriero E;Colonna G;Ianora A;Ciliberto G;Costantini M
通讯作者：
Costantini M
影响因子：
3.2
作者：
Ben-Baruch, Adit
通讯作者：
Ben-Baruch, Adit
与原发性结肠癌细胞相比，转移性结肠癌细胞群含有更多的癌干细胞，对天然杀伤细胞介导的裂解具有更高的敏感性。
影响因子：
2.9
作者：
Kim GR;Ha GH;Bae JH;Oh SO;Kim SH;Kang CD
通讯作者：
Kang CD
影响因子：
4.6
作者：
Molyneaux, KA;Zinszner, H;Lehmann, R
通讯作者：
Lehmann, R
影响因子：
3.8
作者：
Cotte E;Villeneuve L;Passot G;Boschetti G;Bin-Dorel S;Francois Y;Glehen O;French Research Group of Rectal Cancer Surgery (GRECCAR)
通讯作者：
French Research Group of Rectal Cancer Surgery (GRECCAR)